MRI Volumetric Analysis in Rett Syndrome
Abstract number :
2.198
Submission category :
5. Neuro Imaging / 5A. Structural Imaging
Year :
2023
Submission ID :
418
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: hajime Narita, MD – Nagoya University Graduate School of Medicine
Takeshi Suzuki, MD,PhD – Okazaki City Hospital; Jun Natsume, MD,PhD – Nagoya University Graduate School of Medicine; Keita Tsujimura, MD,PhD – Nagoya University Neuroscience Institute of the Graduate School of Science; Tadashi Shiohama, MD,PhD – Chiba University Graduate School of Medicine; Masahiro Kawaguchi, MD,PhD – Aichi Children’s Medical and Health Center; Takamasa Mitsumatsu, MD – Nagoya University Graduate School of Medicine; Ryosuke Suzui, MD – Nagoya University Graduate School of Medicine; Fumi Sawamura, MD – Nagoya University Graduate School of Medicine; Anna Shiraki, MD – Nagoya University Graduate School of Medicine; Yuji Ito, MD,PhD – Nagoya University Graduate School of Medicine; Hiroyuki Yamamoto, MD,PhD – Nagoya University Graduate School of Medicine; Tomohiko Nakata, MD,PhD – Nagoya University Graduate School of Medicine; Hiroyuki Kidokoro, MD,PhD – Nagoya University Graduate School of Medicine; Shinji Naganawa, MD,PhD – Nagoya University Graduate School of Medicine
Rationale: Rett syndrome is a progressive neurodevelopmental disorder affecting girls caused by mutations in the MECP2 gene. The prevalence of epilepsy is reported to be 60-90%. While microcephaly is known as a common feature, there are limited reports on the detailed brain structural changes in children. This study aimed to investigate brain volume abnormalities using 3DT1-weighted imaging and examine the correlation of the brain volume abnormalities and clinical characteristics.
Methods: We compared 20 female children with Rett syndrome who underwent head MRI with 25 healthy female children. T1-weighted MPRAGE sequence was performed using a 3T MRI scanner. We used Freesurfer 7 for image analysis to compute the volumes of gray and white matters in the cerebrum, cerebellum, and other brain regions. Clinical severity was assessed using the Clinical Severity Score (CSS). Statistical analyses included covariance analysis with age as a covariate for brain volume and partial correlation analysis controlling for age to examine the correlation with clinical severity. Multiple comparison corrections were applied using the false discovery rate (FDR).
Results: The median age of the patients with Rett syndrome was eight years (range 3-18 years) and that of the healthy controls was nine years (range 3-18 years). Seventeen out of 20 patients had epilepsy (16 patients with focal epilepsy, 0 with generalized epilepsy and one with unknown epilepsy type). The median age of epilepsy onset was three years. Significant volume reductions were observed in all brain regions in patients with Rett syndrome, including the cerebral cortex, cerebral white matter, subcortical gray matter, cerebellum, and brainstem. After the correction by intracranial volume, the volume reduction was prominent in the cerebral cortex compared to the cerebral white matter. The volume reduction was consistently seen in patients regardless of age. In comparison of the right-left volumes of the paired structures, patients with Rett syndrome showed larger asymmetry in the inferior parietal lobule, precentral gyrus and frontal pole than that of controls. In comparison of the brain volume and clinical characteristics, negative correlations were observed in the volumes of multiple regions with total CSS and gross motor function. On the other hand, no significant correlations were found between the brain volume and fine motor and communicative functions, age of epilepsy onset, or duration of epilepsy.
Conclusions: The present study revealed widespread reduction of the brain volumes in multiple regions, especially in the cerebral cortices. Significant negative correlation was observed between volumes and clinical severity in multiple regions. Studies using model mice of Rett syndrome have reported reduction of the brain volumes in multiple regions, possibly due to abnormalities in neurodevelopment. Our findings support the brain structural abnormalities observed in the mouse models and provide new insights for diagnosis and evaluation of drug efficacy in clinical medicine.
Funding: There are no funds received.
Neuro Imaging